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The Pediatric Lupus Nephritis Mycophenolate Mofetil (PLUMM) Study (PLUMM)
Catherine Robben - catherine.robben@cchmc.org
ALL
8 years to 20 years old
PHASE2
NCT05538208
Inclusion
• Male or female aged 8 to \< 21 years;
• Must meet Classification Criteria for SLE as per the criteria of the American College of Rheumatology (ACR)/ European League Against Rheumatism
• Diagnosed with proliferative LN as per the International Society of Nephrology/Renal Pathology Society4 based on kidney biopsy done within 90 days prior to enrollment into the study; Subjects may have been previously diagnosed with LN. For study inclusion, the kidney biopsy must be interpreted as one of the following classes: Class 3, Class 3/5, Class 4, or Class 4/5.
• Treatment of LN with twice daily MMF as per the decision of the treating physician. The subject will have taken MMF as prescribed by their treating physician for a minimum of 4 days (or 8 doses).
• Subject tolerates MMF as per the treating physician's opinion;
• Able to swallow MMF tablets and capsules;
• If subject is treated with belimumab, must be IV or SQ;
• Subjects who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures;
• Evidence of a personally signed and dated Informed Consent document and Assent document (as appropriate) indicating that the subject and a legally acceptable representative/ parent(s)/legal guardian has been informed of all pertinent aspects of the study.
• Parent or legal guardian must have a smart phone available and able to support the PLUMM smart phone application.
• Must be able to complete study questionnaires in English or Spanish.
• Perceived or stated inability to adhere to the study protocol;
• Hypersensitivity to MMF or any component of the drug product;
• Presence of features (from SLE or other chronic disease) that a-priori suggest that the subject benefits from other therapies than that suggested or allowable by the study protocol; These disease features include but are not limited to severe, progressive, or uncontrolled hepatic, hematologic, gastrointestinal, metabolic, endocrine, pulmonary, cardiac or neurologic disease.
• History of other kidney disease besides LN or prior to the diagnosis of SLE;
• Need for renal replacement therapy within 2 weeks from Baseline Subjects can have required short-term renal replacement therapy prior to Baseline, for example due to preceding acute kidney injury.
• Infections:
• Untreated latent or active tuberculosis (TB);
• Chronic infections requiring treatment;
• A subject known to be infected with Human Immunodeficiency Virus (HIV), Hepatitis B;
• Diagnosis of any infection requiring hospitalization, parenteral antimicrobial therapy or judged to be opportunistic by the investigator within 4 weeks prior to Baseline visit;
• Any treated infections within 2 weeks of Baseline visit;
• History of infected joint prosthesis with prosthesis still in situ;
• Blood dyscrasias, including:
• Hemoglobin \<8.5 g/dL or Hematocrit \<22%;
• White Blood Cell count \<2.6 x 109/L;
• Neutrophil count \<1.2 x 109/L;
• Platelet count \<100 x 109/L;
• Lymphocyte count \<0.5 x 109/L.
• 8\) Estimated glomerular filtration rate \[GFR\] \<40 mL/min/1.73 m2 calculated using the CKiD U25 equation (see Appendix 4);
• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \>1.5 times the upper limit of normal;
• Vaccinated or exposed to a live or attenuated vaccine within the 4 weeks prior to Baseline visit;
• History or current symptoms suggestive of lymphoproliferative disorders (e.g., Epstein Barr Virus \[EBV\] related lymphoproliferative disorder, lymphoma, leukemia, myeloproliferative disorders, or multiple myeloma);
• Current malignancy or history of any malignancy with the exception of adequate treated or excised basal cell or squamous cell or cervical cancer in situ;
• Recent (within 4 weeks prior to Baseline visit) significant trauma or major surgery;
• Herbal supplements with pharmaceutical properties must be discontinued at least 1week prior to Baseline visit, unless there are sufficient data available regarding the duration of an herbal medication's pharmacokinetic and pharmacodynamic effects to allow a shorter or longer washout to be specified (e.g., 5 half-lives).
• Oral or intravenous cyclophosphamide must be discontinued 12 weeks prior to Baseline visit
• Use of prohibited prescription medication as listed in Appendix 3 within the specified time frame prior to Baseline visit
• Participation in other studies involving investigational drug(s) within 4 weeks or 5 half-lives (whichever is longer) prior to Baseline visit and/or during study participation; Exposure to investigational biologics should be discussed with the Sponsor.
• Pregnant female subjects; breastfeeding female subjects; male subjects with partners currently pregnant; male subjects able to father children and female subjects of childbearing potential who are unwilling or unable to use two highly effective methods of contraception or are abstinent for the duration of the study;
• Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for entry into this study.
• Male or female aged 8 to \< 21 years;
• Must meet Classification Criteria for SLE as per the criteria of the American College of Rheumatology (ACR)/ European League Against Rheumatism
• Diagnosed with proliferative LN as per the International Society of Nephrology/Renal Pathology Society4 based on kidney biopsy done within 90 days prior to enrollment into the study; Subjects may have been previously diagnosed with LN. For study inclusion, the kidney biopsy must be interpreted as one of the following classes: Class 3, Class 3/5, Class 4, or Class 4/5.
• Treatment of LN with twice daily MMF as per the decision of the treating physician. The subject will have taken MMF as prescribed by their treating physician for a minimum of 4 days (or 8 doses).
• Subject tolerates MMF as per the treating physician's opinion;
• Able to swallow MMF tablets and capsules;
• If subject is treated with belimumab, must be IV or SQ;
• Subjects who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures;
• Evidence of a personally signed and dated Informed Consent document and Assent document (as appropriate) indicating that the subject and a legally acceptable representative/ parent(s)/legal guardian has been informed of all pertinent aspects of the study.
• Parent or legal guardian must have a smart phone available and able to support the PLUMM smart phone application.
• Must be able to complete study questionnaires in English or Spanish.
Exclusion Criteria:
• Perceived or stated inability to adhere to the study protocol;
• Hypersensitivity to MMF or any component of the drug product;
• Presence of features (from SLE or other chronic disease) that a-priori suggest that the subject benefits from other therapies than that suggested or allowable by the study protocol; These disease features include but are not limited to severe, progressive, or uncontrolled hepatic, hematologic, gastrointestinal, metabolic, endocrine, pulmonary, cardiac or neurologic disease.
• History of other kidney disease besides LN or prior to the diagnosis of SLE;
• Need for renal replacement therapy within 2 weeks from Baseline Subjects can have required short-term renal replacement therapy prior to Baseline, for example due to preceding acute kidney injury.
• Infections:
• Untreated latent or active tuberculosis (TB);
• Chronic infections requiring treatment;
• A subject known to be infected with Human Immunodeficiency Virus (HIV), Hepatitis B;
• Diagnosis of any infection requiring hospitalization, parenteral antimicrobial therapy or judged to be opportunistic by the investigator within 4 weeks prior to Baseline visit;
• Any treated infections within 2 weeks of Baseline visit;
• History of infected joint prosthesis with prosthesis still in situ;
• Blood dyscrasias, including:
• Hemoglobin \<8.5 g/dL or Hematocrit \<22%;
• White Blood Cell count \<2.6 x 109/L;
• Neutrophil count \<1.2 x 109/L;
• Platelet count \<100 x 109/L;
• Lymphocyte count \<0.5 x 109/L.
• 8\) Estimated glomerular filtration rate \[GFR\] \<40 mL/min/1.73 m2 calculated using the CKiD U25 equation (see Appendix 4);
• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \>1.5 times the upper limit of normal;
• Vaccinated or exposed to a live or attenuated vaccine within the 4 weeks prior to Baseline visit;
• History or current symptoms suggestive of lymphoproliferative disorders (e.g., Epstein Barr Virus \[EBV\] related lymphoproliferative disorder, lymphoma, leukemia, myeloproliferative disorders, or multiple myeloma);
• Current malignancy or history of any malignancy with the exception of adequate treated or excised basal cell or squamous cell or cervical cancer in situ;
• Recent (within 4 weeks prior to Baseline visit) significant trauma or major surgery;
• Herbal supplements with pharmaceutical properties must be discontinued at least 1week prior to Baseline visit, unless there are sufficient data available regarding the duration of an herbal medication's pharmacokinetic and pharmacodynamic effects to allow a shorter or longer washout to be specified (e.g., 5 half-lives).
• Oral or intravenous cyclophosphamide must be discontinued 12 weeks prior to Baseline visit
• Use of prohibited prescription medication as listed in Appendix 3 within the specified time frame prior to Baseline visit
• Participation in other studies involving investigational drug(s) within 4 weeks or 5 half-lives (whichever is longer) prior to Baseline visit and/or during study participation; Exposure to investigational biologics should be discussed with the Sponsor.
• Pregnant female subjects; breastfeeding female subjects; male subjects with partners currently pregnant; male subjects able to father children and female subjects of childbearing potential who are unwilling or unable to use two highly effective methods of contraception or are abstinent for the duration of the study;
• Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for entry into this study.
DRUG: Mycophenolate Mofetil, DRUG: Mycophenolate Mofetil
Lupus Nephritis
Supraspinal Processing of Sensory Aspects of Pain (SCP)
Catherine Jackson - catherine.jackson@cchmc.org
ALL
10 years to 17 years old
NA
NCT05814497
Inclusion Criteria:
* Patients will need a diagnosis of a chronic pain derived congruent with ICD-11 criteria related to headache (migraine, daily headache), abdominal (FAPD), localized MSK (single limb/joint, low back or chest pain), diffuse MSK (widespread MSK pain), or CRPS
* If on medications, they need to be on stable doses of prescribed pain and/or psychiatric medications for 4 weeks before the baseline study visit.
* Male or female, age 10 -17 (inclusive)
* English speaking, able to complete interviews and questionnaires in English
Exclusion Criteria:
* Weight/size incompatible with MRI scanner
* Orthodontic braces, metallic or electronic implants, or other metal objects in the body which obscure or interfere with the MRI, or pose a risk from heating, movement, or malfunction in the MRI environment
* Claustrophobia
* Youth who are pregnant
* Any comorbid rheumatic disease, diagnosis of epilepsy, other neurological diseases, or medical condition (e.g. diabetes, cancer, IBD)
* Present psychiatric disease as defined by DSM IV (e.g. psychosis, bipolar disorder, major depression, generalized anxiety disorder), alcohol or drug dependence, or documented developmental delays or impairments (e.g., autism, cerebral palsy, ADHD, or mental retardation) that, in the opinion of the investigator, would interfere with adherence to study requirements or safe participation in the study
* Skin conditions or past skin damage on the arms or legs in or near sites of sensory testing
* Outside the age range (9 years old or younger; 18 years or older) at the time of consent
* History of \> 1 month opioid treatment. OTHER: Multisensory Task, OTHER: Graphesthesia, OTHER: Divided attention
Migraine in Children, Complex Regional Pain Syndromes, Musculoskeletal Pain, Functional Abdominal Pain Syndrome, Fibromyalgia
chronic pain
Descartes-08 for Children, Adolescents, and Young Adults With Autoimmune Disorders
Alexandra Duell - alexandra.duell@cchmc.org
ALL
12 years and over
PHASE1
NCT07089121
Inclusion Criteria:
* At least age 12
* definitive diagnosis of childhood-onset systemic lupus erythematous, juvenile Myasthenie gravis, juvenile dermatomyositis and AAV
* Signs and symptoms of moderate disease
* History of systemic treatment
* Parent/Guardian/Patient must be able to give written informed consent
Exclusion Criteria:
* Major chronic illness that is not well managed at the time of study entry and in the opinion of the investigator may increase the risk to the patient;
* Abnormal PT/INR or PTT increased \> 1.5-fold or patient is on anticoagulation therapy (except in cases of elevated PTT with documented lupus anticoagulant; or in patients who have been on stable doses of anticoagulation therapy for more than 6 months of VTE diagnosis; or in patients on stable doses of anticoagulation therapy for at least 8 weeks of atrial fibrillation diagnosis; these conditions will not be exclusionary unless, in the investigator's opinion, they make participation in the study unsafe);
* ANC \< 1000 cells/microliter ;
* Hemoglobin \< 8.0 g/dL ;
* Platelets \< 50,000/mm3 (NOTE: platelet transfusions are permissible);
* ALT and/or AST with GGT ≥ 3× upper limit of normal
* Creatine Clearance less than 30mL/min /1.73 m2;
* History of primary immunodeficiency, organ, or allogeneic bone marrow transplant;
* Patients must be seronegative for hepatitis B surface antigen;
* Patients must be seronegative for hepatitis C antibody. If hepatitis C antibody test is positive, then patients must be tested for the presence of viremia by RT-PCR and must be HCV RNA negative;
* History of positive HIV or positive HIV at screening;
* Active tuberculosis or positive QuantiFERON test at screening;
* Any other laboratory abnormality that, in the opinion of the investigator, may jeopardize the subject's ability to participate in the study; 23. Any active significant cardiac or pulmonary disease not related to the primary indication as determined by principal investigator and medical monitor Note: Patients with asthma and COPD controlled with inhaled medications are allowed; 24. Any arterial or venous thromboembolic events in the past 3 months; 25. History of malignancy that required treatment in the past 3 years except for successfully-treated squamous cell and/or basal cell carcinoma of the skin and/or breast or colon cancer that is surgically removed and did not require adjuvant chemotherapy or radiotherapy; 26. Treatment with any investigational agent within 4 weeks of screening or 5 half-lives of the investigational drug (whichever is longer); 27. Receipt of a live vaccination within 4 weeks prior to baseline (Day 1) or intent to receive live vaccination during the study (Note: mRNA-based vaccines such as those against SARS-CoV-2 are not considered live; likewise, the Janssen Covid-19 vaccine is not live); 28. History of significant recurrent infections or any active infection that may interfere with the patient's participation in the opinion of the investigator; 29. Any known psychiatric illness that may interfere with the patient's participation in the study in the opinion of the investigator. DRUG: Descartes-08
Childhood-onset Systemic Lupus Erythematous, ANCA-Associated Vasculitis (AAV), Juvenile Myasthenia Gravis, Juvenile Dermatomyositis
ATHN Transcends: A Natural History Study of Non-Neoplastic Hematologic Disorders
Kenzie Nolte - mackenzie.nolte@cchmc.org
ALL
NCT04398628
Participants who meet the following inclusion criteria and none of the exclusion criteria are eligible for enrollment in one of the open disease-specific arms.
• Any age
• Having a congenital or acquired blood disorder; or
• Having a bleeding phenotype as indicated by an age adjusted abnormal ISTH Bleeding Assessment Tool score with an unknown diagnosis; or
• Connective tissue disorder with bleeding tendency as indicated by an age adjusted abnormal ISTH Bleeding Assessment Tool score.
• Eligible for a currently active disease-specific arm.
• Concurrent enrollment in the ATHNdataset or current ATHNdataset participant.
• Factor VIII or factor IX activity \<50%, without another explanation for low clotting factor other than congenital hemophilia or being a known carrier for congenital hemophilia; OR
• Carrier for congenital hemophilia with a factor VIII \>=50% or factor IX activity \>=50% with or without a bleeding phenotype as indicated by an ISTH Bleeding Assessment Tool score of ≥4 for adult males, ≥6 for adult females, or ≥3 for children younger than 18 years OR
• Known congenital hemophilia that have a factor level \>50% after receiving vector, OR 4. Acquired hemophilia.
• Abnormalities of platelet function a. Glanzmann thrombasthenia (GPIIb or GPIIIa) b. Bernard-Soulier syndrome (GPIbalpha, GPIbbeta, or GPIX)
• Abnormalities of platelet granules
• Abnormalities of platelet signal transduction
• Abnormalities of platelet secretion
• Collagen Receptor Defect
• ADP Receptor Defect
• Thromboxane Receptor Defect
• Giant Platelet Disorder
• Abnormalities in platelet aggregation testing due to another or unknown cause (not drug related)
• PAI-1 deficiency
• Factor I, II, V, VII, X, XI, XIII deficiencies
• Combined FV and FVIII deficiency
• Plasminogen deficiency
• Decreased tissue plasminogen activator
• Afibrinogenemia/hypofibrinogenemia/dysfibrinogenemia
• Thrombotic Thrombocytopenia Purpura or Congenital Hemolytic Uremic Syndrome
• Wiskott-Aldrich
• Methylenetetrahydrofolate Reductase Deficiency
• Have a bleeding phenotype as indicated by an ISTH Bleeding Assessment Tool score of ≥4 for adult males, ≥6 for adult females, or ≥3 for children younger than 18 years with an unknown diagnosis, OR
• Connective tissue disorder with bleeding tendency as indicated by an ISTH Bleeding Assessment Tool score of ≥4 for adult males, ≥6 for adult females, or ≥3 for children younger than 18 years.
• Diagnosis of congenital hemophilia A (FVIII \<40%) or hemophilia B (FIX \<40% or below lower limit for age)
• Age \<18 years at time of enrollment
• Parent or authorized guardian or legally authorized representative (LAR) can provide informed consent
• Care established at one of the ATHN Transcends participating HTCs
• Clotting Factor Concentrate (CFC) exposure, fresh frozen plasma (FFP), cryoprecipitate, and single donor platelets \<3 exposure days (ED) Exclusion Criteria
• Concomitant diagnosis with another bleeding disorder
• History of a confirmed, positive inhibitor INHIBIT Module
• Concomitant diagnosis with bleeding disorder other than hemophilia A
• Immune disorder
• Previous history or presence of factor VIII inhibitor. A confirmed, positive inhibitor is defined as two consecutive positive inhibitor titers (≥ 0.6 BU) that result in changes in treatment recommendations. Efanesoctocog alfa (ALTUVIIIO®) Module Inclusion criteria:
• Ability of the potential participant's legally authorized representative (e.g., their parent or legal guardian) to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use confidential health information in accordance with national and local participant privacy regulation.
• People with severe HA with a baseline FVIII activity of less than 1%. (While inclusion for participation in ATHN Transcends lists \<5% FVIII activity, this proposed module will limit enrollment to people with FVIII activity levels of \<1%.) Other severities may be included per ATHN Transcends PI approval.
• \<18 years of age.
• No history of a confirmed, positive FVIII inhibitor.
• Sex assigned at birth of male, female, or intersex.
• Participants should have no more than three (3) exposure days of blood products (fresh frozen plasma, cryoprecipitate, or platelets), no more than three (3) doses of any FVIII concentrate other than efanesoctocog alfa, and up to three (3) doses of efanesoctocog alfa prior to enrollment.
• Site PI confirmed all inclusion criteria has been met. Exclusion criteria:
• Not meeting all the inclusion criteria; confirmed by site PI.
• Any exposure to blood products or FVIII replacement products except as described in the inclusion criteria.
• History of positive inhibitor testing.
• History of hypersensitivity reactions associated with efanesoctocog alfa administration.
• Other coagulation disorder(s) in addition to Hemophilia A.
• Any concurrent clinically significant major disease such as cancer that, in the opinion of the investigator, would make the participant unsuitable for enrollment.
• Concurrent systemic treatment with chemotherapy and/or other immunosuppressant medications. Use of corticosteroids for the treatment of asthma or management of acute allergic or otherwise life-threatening episodes is allowed except for systemic corticosteroid treatment given to children daily or on an alternate day schedule at \> 2 mg/kg/day of prednisone or its equivalent or \> 20 mg/day if the duration is longer than 14 days.
• Enrollment in a concurrent clinical interventional drug study.
• Intake of an Investigational Medicinal Product within three (3) months prior to inclusion in this study.
• Inability to comply with study requirements.
• Other, unspecified reasons that, in the investigator's opinion, make the participant unsuitable for enrollment. Hemophilia Natural History Arm Inclusion Criteria
• Congenital or acquired hemophilia A or B of any severity with or without inhibitors receiving a current therapy, a non-factor product, or for whom use of a non-factor product is a possibility, OR
• Females of any age, with confirmed congenital hemophilia A or B carrier status with genetic mutational analysis and any factor level. Exclusion Criteria
• Presence of any known bleeding disorder other than congenital hemophilia A or B
• Presence of concurrent hemophilia and a second hemostatic defect (low von Willebrand Factor (vWF) without vWD diagnosis is not excluded)
• Unable or unwilling to comply with the study arm protocol. Nonacog beta pegol (Rebinyn®) Module
• Has provided signed written consent for the nonacog beta pegol (Rebinyn®)Module before any study-related activities.
• Male participants, at any age with hemophilia B, naïve or minimally exposed (up to 3 EDs) to nonacog beta pegol treatment at time of study enrollment. Additional doses may be allowable per ATHN Transcends PI approval.
• Decision to initiate continuous prophylaxis treatment with commercially available nonacog beta pegol has been made by the participant(s)/Legally Authorized Representative(s) (LAR(s)) and the treating physician before and independently from the decision to include the participant in this study.
• Previous participation in this study. Participation is defined as having given informed consent in this study.
• Mental incapacity, unwillingness or language barriers precluding adequate understanding or cooperation, including a diagnosis or suspicion of attention deficit hyperactivity disorder (ADHD) or autism spectrum disorder (ASD) per the discretion of the Principal Investigator.
• Known or suspected hypersensitivity to nonacog beta pegol or related products.
• Clinical suspicion or presence of FIX inhibitor at time of inclusion.
• Inability or unwillingness to undergo neurological assessment/structured developmental history. Emicizumab (Hemlibra®) Module
• Participant currently treated with emicizumab (Hemlibra®)
• Currently enrolled in the Hemophilia Natural History Arm of ATHN Transcends
• Congenital hemophilia A or B of any severity with or without inhibitors receiving a current therapy, a non-factor product, or for whom use of a non-factor product is a possibility
• Age 18 years of age or older
• English speaking
• Presence of any known bleeding disorder other than congenital hemophilia A or B;
• Presence of concurrent hemophilia and a second hemostatic defect (low von Willebrand Factor (vWF) without vWD diagnosis is not excluded); and
• Unable or unwilling to comply with the study arm protocol Hemophilia Gene Therapy Outcomes Arm Inclusion Criteria
• Hemophilia A or B of any severity with or without inhibitors having received or will receive a hemophilia gene transfer product in the next 6 months.
• Age 18 years and older.
• Able to give informed consent. Exclusion Criteria None Etranacogene dezaparvovec (HEMGENIX®) Module
• Age 18 years of age or older
• Treatment with commercial etranacogene dezaparvovec (HEMGENIX®)
• Have provided signed written informed consent within 3 months before or within 6 months after etranacogene dezaparvovec (HEMGENIX®) treatment, or within 6 months of when the study is initiated at the treating site. FIX Prophylaxis Cohort
• Age 18 years of age or older
• Treatment with FIX prophylaxis therapy
• Has provided signed written consent at any time for ATHN Transcends Study Exclusion Criteria, both cohorts: 1\. Have been treated with etranacogene dezaparvovec in a clinical trial prior to commercial availability. These patients are still eligible for enrollment in the Gene Therapy Outcomes Arm, and their data may be collected for separate analysis. Congenital Platelet Disorders Arm Inclusion Criteria
• Platelet adhesion defect
• Bernard Soulier syndrome (Defective GPIb-IX-V receptor, impaired adhesion to vWF)
• Velocardio-facial syndrome/DiGeorge syndrome (Defective GPIb-IX-V receptor)
• Platelet type vWD (Defective GPIb-IX-V, gain of function interaction between vWF-GP1bα)
• Platelet aggregation defect
• Glanzmann thrombasthenia (Defective integrin αIIbβ3 (GPIIb/IIIa)
• Platelet aggregation defect, NOS
• Agonist receptor defects
• Epinephrine
• ADP
• Collagen
• Thromboxane A2
• Platelet signaling defects
• Cyclooxygenase deficiency (PTGS1 mutation)
• Phospholipase A2 deficiency
• Thromboxane synthase deficiency (TBXAS1 mutation)
• G protein activation defect (GNAS mutation)
• Scott syndrome (defect in phosphatidyl serine translocation)
• Platelet Granule disorders
• Dense granule storage pool disorder * Hermansky Pudlak syndrome * Chediak Higashi syndrome * Griscelli syndrome
• Alpha granule storage pool disorder * Grey platelet syndrome * Arthrogryposis-Renal Dysfunction-Cholestasis (ARC) syndrome * Quebec platelet disorder * Paris-Trousseau syndrome
• Combined alpha delta granule deficiency
• Platelet cytoskeletal structure defects
• Wiskott Aldrich syndrome
• MYH9 associated disorders (myosin heavy chain) * May Hegglin syndrome * Fechtner syndrome * Sebastian syndrome * Epstein syndrome
• Other mutations * FLNA mutations (Filamin) * DIAPH1 (Actin and microtubules) * ACTN1 (alpha actinin) * TPM4 (tropomyosin) * TUBB1 (beta tubulin)
• Other Congenital thrombocytopenias
• Familial platelet disorders and predisposition to AML (RUNX1)
• X linked thrombocytopenia with dyserythropoiesis (GATA1)
• Congenital amegakaryocytic thrombocytopenia (MPL) Exclusion Criteria
• Diagnosis of von Willebrand Disease (Meeting the definition of vWD or low vWF per most recent international guidelines)
• Diagnosis of Hemophilia A or Hemophilia B (Factor VIII or IX ≤ 40%) Glanzmann Thrombasthenia (GT) Module Inclusion Criteria
• Participant has signed the informed consent/assent form
• Participant has flow cytometry or aggregometry or genetics confirmed GT
• Participant is willing to perform study procedures, including daily bleed tracking for 3 months and further if requested
• Participants are 2 years or older at time of consent Exclusion Criteria None
Inclusion Criteria:
• Any age
• Having a congenital or acquired blood disorder; or
• Having a bleeding phenotype as indicated by an age adjusted abnormal ISTH Bleeding Assessment Tool score with an unknown diagnosis; or
• Connective tissue disorder with bleeding tendency as indicated by an age adjusted abnormal ISTH Bleeding Assessment Tool score.
• Eligible for a currently active disease-specific arm.
• Concurrent enrollment in the ATHNdataset or current ATHNdataset participant.
Exclusion Criteria:
1\. Does not qualify for inclusion in a currently activedisease-specific arm; participants may be eligible to enroll as future cohorts and arms are activated; 2. Unable to give informed consent or assent 3. Unwilling to perform study procedures
Cohort Participant Selection
Each participant is to be enrolled in the cohort for which they qualify as defined below.
Hemophilia Cohort
Inclusion Criteria:
Participants who meet any of the following inclusion criteria are eligible for enrollment into this cohort:
• Factor VIII or factor IX activity \<50%, without another explanation for low clotting factor other than congenital hemophilia or being a known carrier for congenital hemophilia; OR
• Carrier for congenital hemophilia with a factor VIII \>=50% or factor IX activity \>=50% with or without a bleeding phenotype as indicated by an ISTH Bleeding Assessment Tool score of ≥4 for adult males, ≥6 for adult females, or ≥3 for children younger than 18 years OR
• Known congenital hemophilia that have a factor level \>50% after receiving vector, OR 4. Acquired hemophilia.
Exclusion Criteria:
None
Von Willebrand Disease Cohort
Inclusion Criteria:
Participants who meet the following inclusion criteria are eligible for enrollment into this cohort:
1\. Meeting the definition of VWD or low VWF per most recent international guidelines
Exclusion Criteria:
None
Congenital Platelet Disorders Cohort
Inclusion Criteria:
Participants who meet the following inclusion criteria are eligible for enrollment into this cohort:
• Abnormalities of platelet function a. Glanzmann thrombasthenia (GPIIb or GPIIIa) b. Bernard-Soulier syndrome (GPIbalpha, GPIbbeta, or GPIX)
• Abnormalities of platelet granules
• Abnormalities of platelet signal transduction
• Abnormalities of platelet secretion
• Collagen Receptor Defect
• ADP Receptor Defect
• Thromboxane Receptor Defect
• Giant Platelet Disorder
• Abnormalities in platelet aggregation testing due to another or unknown cause (not drug related)
Exclusion Criteria:
1\. Platelet disorders secondary to medications or other substances
Rare Disorders Cohort
Inclusion Criteria:
Participants who meet the following inclusion criteria are eligible for enrollment into this cohort:
1\. Have an established Rare Coagulation Disorder (RCD) diagnosis of one of the following:
• PAI-1 deficiency
• Factor I, II, V, VII, X, XI, XIII deficiencies
• Combined FV and FVIII deficiency
• Plasminogen deficiency
• Decreased tissue plasminogen activator
• Afibrinogenemia/hypofibrinogenemia/dysfibrinogenemia
• Thrombotic Thrombocytopenia Purpura or Congenital Hemolytic Uremic Syndrome
• Wiskott-Aldrich
• Methylenetetrahydrofolate Reductase Deficiency
Exclusion Criteria:
None
Bleeding NOS Cohort
Inclusion Criteria:
Participants who meet the following inclusion criteria are eligible for enrollment into this cohort:
• Have a bleeding phenotype as indicated by an ISTH Bleeding Assessment Tool score of ≥4 for adult males, ≥6 for adult females, or ≥3 for children younger than 18 years with an unknown diagnosis, OR
• Connective tissue disorder with bleeding tendency as indicated by an ISTH Bleeding Assessment Tool score of ≥4 for adult males, ≥6 for adult females, or ≥3 for children younger than 18 years.
Exclusion Criteria:
None
Thrombosis/Thrombophilia Cohort
Inclusion Criteria
Participants who meet the following inclusion criteria are eligible for enrollment into this cohort:
1\. Have a prior history of arterial or venous thrombosis. 2. Participants with a known congenital or acquired thrombophilia with or without thrombosis.
a. Common congenital thrombophilias: i. Protein C deficiency ii. Protein S deficiency iii. Antithrombin deficiency iv. Factor V Leiden v. Prothrombin gene mutation b. Rare genetic factors i. Hyperhomocysteinemia c. Indeterminate genetic factors i. Elevated factor VIII ii. Elevated factor IX iii. Elevated factor XI iv. Elevated lipoprotein (a) d. Acquired thrombophilias i. Lupus anticoagulant ii. Anti-cardiolipin antibodies/Beta2 glycoprotein antibodies iii. Antiphospholipid syndrome
Exclusion Criteria Acquired thrombophilia secondary to medications (birth control pills or hormone replacement therapy), overweight or obesity, smoking, cancer, pregnancy, surgery, injury, prolonged inactivity/bedrest, heart failure, inflammatory bowel disease, or kidney disease
Non-Neoplastic Hematologic Conditions Cohort
Inclusion Criteria
Participants who meet the following inclusion criteria are eligible for enrollment into this cohort:
1\. Having any congenital or acquired non-neoplastic hematologic disorder not included in any other cohort
Exclusion Criteria None
Arm/Module Participant Selection
Previously Untreated Patients Arm
Inclusion Criteria:
• Diagnosis of congenital hemophilia A (FVIII \<40%) or hemophilia B (FIX \<40% or below lower limit for age)
• Age \<18 years at time of enrollment
• Parent or authorized guardian or legally authorized representative (LAR) can provide informed consent
• Care established at one of the ATHN Transcends participating HTCs
• Clotting Factor Concentrate (CFC) exposure, fresh frozen plasma (FFP), cryoprecipitate, and single donor platelets \<3 exposure days (ED) Exclusion Criteria
• Concomitant diagnosis with another bleeding disorder
• History of a confirmed, positive inhibitor INHIBIT Module
Inclusion Criteria:
1\. Diagnosis of severe factor VIII deficiency with baseline factor VIII level \<1% 2. Initiating or plan to initiate prophylaxis with emicizumab or factor replacement 3. Factor concentrate exposure, Fresh Frozen Plasma (FFP), cryoprecipitate, and single donor platelets ≤3 EDs 4. ≤5 years of age
Exclusion Criteria
• Concomitant diagnosis with bleeding disorder other than hemophilia A
• Immune disorder
• Previous history or presence of factor VIII inhibitor. A confirmed, positive inhibitor is defined as two consecutive positive inhibitor titers (≥ 0.6 BU) that result in changes in treatment recommendations. Efanesoctocog alfa (ALTUVIIIO®) Module Inclusion criteria:
• Ability of the potential participant's legally authorized representative (e.g., their parent or legal guardian) to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use confidential health information in accordance with national and local participant privacy regulation.
• People with severe HA with a baseline FVIII activity of less than 1%. (While inclusion for participation in ATHN Transcends lists \<5% FVIII activity, this proposed module will limit enrollment to people with FVIII activity levels of \<1%.) Other severities may be included per ATHN Transcends PI approval.
• \<18 years of age.
• No history of a confirmed, positive FVIII inhibitor.
• Sex assigned at birth of male, female, or intersex.
• Participants should have no more than three (3) exposure days of blood products (fresh frozen plasma, cryoprecipitate, or platelets), no more than three (3) doses of any FVIII concentrate other than efanesoctocog alfa, and up to three (3) doses of efanesoctocog alfa prior to enrollment.
• Site PI confirmed all inclusion criteria has been met. Exclusion criteria:
• Not meeting all the inclusion criteria; confirmed by site PI.
• Any exposure to blood products or FVIII replacement products except as described in the inclusion criteria.
• History of positive inhibitor testing.
• History of hypersensitivity reactions associated with efanesoctocog alfa administration.
• Other coagulation disorder(s) in addition to Hemophilia A.
• Any concurrent clinically significant major disease such as cancer that, in the opinion of the investigator, would make the participant unsuitable for enrollment.
• Concurrent systemic treatment with chemotherapy and/or other immunosuppressant medications. Use of corticosteroids for the treatment of asthma or management of acute allergic or otherwise life-threatening episodes is allowed except for systemic corticosteroid treatment given to children daily or on an alternate day schedule at \> 2 mg/kg/day of prednisone or its equivalent or \> 20 mg/day if the duration is longer than 14 days.
• Enrollment in a concurrent clinical interventional drug study.
• Intake of an Investigational Medicinal Product within three (3) months prior to inclusion in this study.
• Inability to comply with study requirements.
• Other, unspecified reasons that, in the investigator's opinion, make the participant unsuitable for enrollment. Hemophilia Natural History Arm Inclusion Criteria
• Congenital or acquired hemophilia A or B of any severity with or without inhibitors receiving a current therapy, a non-factor product, or for whom use of a non-factor product is a possibility, OR
• Females of any age, with confirmed congenital hemophilia A or B carrier status with genetic mutational analysis and any factor level. Exclusion Criteria
• Presence of any known bleeding disorder other than congenital hemophilia A or B
• Presence of concurrent hemophilia and a second hemostatic defect (low von Willebrand Factor (vWF) without vWD diagnosis is not excluded)
• Unable or unwilling to comply with the study arm protocol. Nonacog beta pegol (Rebinyn®) Module
Inclusion Criteria:
• Has provided signed written consent for the nonacog beta pegol (Rebinyn®)Module before any study-related activities.
• Male participants, at any age with hemophilia B, naïve or minimally exposed (up to 3 EDs) to nonacog beta pegol treatment at time of study enrollment. Additional doses may be allowable per ATHN Transcends PI approval.
• Decision to initiate continuous prophylaxis treatment with commercially available nonacog beta pegol has been made by the participant(s)/Legally Authorized Representative(s) (LAR(s)) and the treating physician before and independently from the decision to include the participant in this study.
Exclusion Criteria:
• Previous participation in this study. Participation is defined as having given informed consent in this study.
• Mental incapacity, unwillingness or language barriers precluding adequate understanding or cooperation, including a diagnosis or suspicion of attention deficit hyperactivity disorder (ADHD) or autism spectrum disorder (ASD) per the discretion of the Principal Investigator.
• Known or suspected hypersensitivity to nonacog beta pegol or related products.
• Clinical suspicion or presence of FIX inhibitor at time of inclusion.
• Inability or unwillingness to undergo neurological assessment/structured developmental history. Emicizumab (Hemlibra®) Module
Inclusion Criteria:
• Participant currently treated with emicizumab (Hemlibra®)
• Currently enrolled in the Hemophilia Natural History Arm of ATHN Transcends
Exclusion Criteria:
1\. Unable or unwilling to comply with the protocol
Distress Module
Inclusion Criteria:
• Congenital hemophilia A or B of any severity with or without inhibitors receiving a current therapy, a non-factor product, or for whom use of a non-factor product is a possibility
• Age 18 years of age or older
• English speaking
Exclusion Criteria:
• Presence of any known bleeding disorder other than congenital hemophilia A or B;
• Presence of concurrent hemophilia and a second hemostatic defect (low von Willebrand Factor (vWF) without vWD diagnosis is not excluded); and
• Unable or unwilling to comply with the study arm protocol Hemophilia Gene Therapy Outcomes Arm Inclusion Criteria
• Hemophilia A or B of any severity with or without inhibitors having received or will receive a hemophilia gene transfer product in the next 6 months.
• Age 18 years and older.
• Able to give informed consent. Exclusion Criteria None Etranacogene dezaparvovec (HEMGENIX®) Module
Inclusion Criteria:
Etranacogene dezaparvovec (HEMGENIX®) Cohort
• Age 18 years of age or older
• Treatment with commercial etranacogene dezaparvovec (HEMGENIX®)
• Have provided signed written informed consent within 3 months before or within 6 months after etranacogene dezaparvovec (HEMGENIX®) treatment, or within 6 months of when the study is initiated at the treating site. FIX Prophylaxis Cohort
• Age 18 years of age or older
• Treatment with FIX prophylaxis therapy
• Has provided signed written consent at any time for ATHN Transcends Study Exclusion Criteria, both cohorts: 1\. Have been treated with etranacogene dezaparvovec in a clinical trial prior to commercial availability. These patients are still eligible for enrollment in the Gene Therapy Outcomes Arm, and their data may be collected for separate analysis. Congenital Platelet Disorders Arm Inclusion Criteria
• Platelet adhesion defect
• Bernard Soulier syndrome (Defective GPIb-IX-V receptor, impaired adhesion to vWF)
• Velocardio-facial syndrome/DiGeorge syndrome (Defective GPIb-IX-V receptor)
• Platelet type vWD (Defective GPIb-IX-V, gain of function interaction between vWF-GP1bα)
• Platelet aggregation defect
• Glanzmann thrombasthenia (Defective integrin αIIbβ3 (GPIIb/IIIa)
• Platelet aggregation defect, NOS
• Agonist receptor defects
• Epinephrine
• ADP
• Collagen
• Thromboxane A2
• Platelet signaling defects
• Cyclooxygenase deficiency (PTGS1 mutation)
• Phospholipase A2 deficiency
• Thromboxane synthase deficiency (TBXAS1 mutation)
• G protein activation defect (GNAS mutation)
• Scott syndrome (defect in phosphatidyl serine translocation)
• Platelet Granule disorders
• Dense granule storage pool disorder * Hermansky Pudlak syndrome * Chediak Higashi syndrome * Griscelli syndrome
• Alpha granule storage pool disorder * Grey platelet syndrome * Arthrogryposis-Renal Dysfunction-Cholestasis (ARC) syndrome * Quebec platelet disorder * Paris-Trousseau syndrome
• Combined alpha delta granule deficiency
• Platelet cytoskeletal structure defects
• Wiskott Aldrich syndrome
• MYH9 associated disorders (myosin heavy chain) * May Hegglin syndrome * Fechtner syndrome * Sebastian syndrome * Epstein syndrome
• Other mutations * FLNA mutations (Filamin) * DIAPH1 (Actin and microtubules) * ACTN1 (alpha actinin) * TPM4 (tropomyosin) * TUBB1 (beta tubulin)
• Other Congenital thrombocytopenias
• Familial platelet disorders and predisposition to AML (RUNX1)
• X linked thrombocytopenia with dyserythropoiesis (GATA1)
• Congenital amegakaryocytic thrombocytopenia (MPL) Exclusion Criteria
• Diagnosis of von Willebrand Disease (Meeting the definition of vWD or low vWF per most recent international guidelines)
• Diagnosis of Hemophilia A or Hemophilia B (Factor VIII or IX ≤ 40%) Glanzmann Thrombasthenia (GT) Module Inclusion Criteria
• Participant has signed the informed consent/assent form
• Participant has flow cytometry or aggregometry or genetics confirmed GT
• Participant is willing to perform study procedures, including daily bleed tracking for 3 months and further if requested
• Participants are 2 years or older at time of consent Exclusion Criteria None
Hematologic Disorder, Bleeding Disorder, Connective Tissue Disorder, Hemophilia, Thrombosis, Von Willebrand Diseases, Thrombophilia, Rare Bleeding Disorder, Platelet Disorder, Factor IX Deficiency, Factor VIII Deficiency, Thalassemia, Sickle Cell Disease
Observational Study of Pediatric Rheumatic Diseases: The CARRA Registry
Megan Quinlan-Waters - megan.quinlan-waters@cchmc.org
ALL
Up to 21 years old
NCT02418442
Inclusion Criteria:
• Onset of rheumatic disease prior to age 16 years for JIA and onset prior to age 19 years for all other rheumatic diseases (see appendix A).
• Subject (and/or parent/legal guardian when required) is able to provide written informed consent and willing to comply with study procedures.
• Subject and/or parent/legal guardian is willing to be contacted in the future by study staff.
Exclusion Criteria:
1\. Greater than 21 years of age at the time of enrollment. Rheumatic Joint Disease
Systemic Arthritis, Oligoarthritis, Polyarthritis (Rheumatoid Factor Negative), Polyarthritis (Rheumatoid Factor Positive), Psoriatic Arthritis, Enthesitis Related Arthritis (ERA), Undifferianted Arthritis, CARRA Consensus Treatment Plans
The BRIDGE Pain Study (BRIDGE)
Megan Kirschman - bridgestudy@cchmc.org
ALL
14 years to 26 years old
NCT07602595
Inclusion Criteria:
* Diagnosis of rheumatic/autoimmune disease/pain condition or surgery prior to age 18; Current age 14 to 26 years; Participant (and parent/legal guardian of participants \< 18 yo) can read and write in English; At least 1 year from diagnosis of pain or rheumatic disease; For individuals with MSK surgical history, at least 1 year after initial surgical intervention; For individuals with rheumatic disease, their disease must be considered inactive
Exclusion Criteria:
* They have active disease, or Other major medical comorbidities have developed after surgery following MSK surgical intervention. OTHER: Not applicable- observational study
Juvenile Idiopathic Arthritis (JIA), Fibromyalgia, Lupus, Scoliosis, Pectus Excavatum, Chronic Pain, Musculoskeletal Pain
A Long-term Extension (LTE) Study of Guselkumab in Pediatric Participants (TRILOGY)
Megan Megan Quinlan-Waters - Megan.Quinlan-Waters@cchmc.org
ALL
3 years and over
PHASE3
NCT06663332
Inclusion Criteria:
* Must have completed the dosing planned in the primary pediatric guselkumab study
* Must have received benefit from continued guselkumab therapy in the opinion of the investigator
* Before enrollment, a participant must be either: (a) Not of childbearing potential, OR (b) Of childbearing potential and not sexually active, practicing abstinence or a highly effective method of contraception and agrees to remain on a highly effective method while receiving study intervention and until 12 weeks after the last dose - the end of relevant systemic exposure
* Parent(s) (or their legally acceptable representative) must sign an informed consent form (ICF) indicating that he or she understands the purpose of, and procedures required for, the study and is willing to allow the child to participate in the study. Assent is required from participants who are capable of understanding the nature of the study, typically those aged 7 years and older, to ensure their willingness to participate. An adolescent who provides assent will have the opportunity to sign an adult ICF upon reaching the age of majority, thereby affirming their understanding of the study's purpose and procedures, as well as their willingness to participate.
Exclusion Criteria:
* Participant is greater than or equal to (\>=) 18 years of age and resides in a country where 2 years have elapsed post marketing authorization for the respective adult indication
* Participant is \<18 years of age and resides in a county where 2 years have elapsed post marketing authorization for the respective pediatric indication
* Are pregnant, nursing, or planning pregnancy or fathering a child
* Have taken any disallowed therapies before the planned first long-term extension (LTE) dose of study intervention
* Employee of the investigator or study site, with direct involvement in the proposed study or other studies under the direction of that investigator or study site, as well as family members of the employees or the investigator
* Any condition for which, in the opinion of the investigator, participation would not be in the best interest of the participant or that could prevent, limit, or confound the protocol-specified assessments DRUG: Guselkumab
Crohns Disease, Colitis, Ulcerative, Arthritis, Psoriatic, Arthritis, Juvenile
Transforming Care for Individuals With Childhood-onset Systemic Lupus Erythematosus (cSLE)
Jainish Patel - jainish.patel@cchmc.org
ALL
12 years to 22 years old
NA
NCT06232304
Inclusion Criteria:
* 1\) be diagnosed with cSLE, meeting the revised American College of Rheumatology Classification Criteria for SLE by age 18 years
* 2\) be between the ages of 12 and 22 years
* 3\) in recognition of the heterogeneity of cSLE symptoms, have elevations in fatigue (i.e., T scores ≥60; or at least moderate symptoms, on the PROMIS measure) OR depressive symptoms (≥5 on the PHQ-9, T Score ≥ 60 on the BDI or CDI II ), OR pain (i.e., average pain ≥3 out of 10 on the Pain VAS)
* 4\) have English language proficiency (their primary caregiver can have English or Spanish language proficiency for the child to enroll)
* 5\) those under age 18 years (US), or 16 years (Canada) must have a consenting caregiver
Exclusion Criteria:
* 1\) other chronic medical conditions (e.g., juvenile arthritis)
* 2\) a documented developmental delay, severe cognitive impairment, or thought disorder
* 3\) an untreated major psychiatric illness (e.g., bipolar disorder, psychosis, severe depression (PHQ9 score ≥21, BDI/CDI II \> 90) or active suicidal ideation (SI), based on the Pediatric Health Questionnaire (PHQ-9) items plus clinical interview; see Measures section) BEHAVIORAL: TEACH
Systemic Lupus Erythematosus of Childhood (Disorder)
lupus, depression, depressive symptoms, fatigue, pain, SLE, rheumatic disease, rheumatology, cognitive behavioral, Childhood-onset Systemic Lupus Erythematosus, cSLE, Implementation, Coping skills, Mindfulness
Heart Institute Biobank & Registry for Adult Congenital Heart Disease and Related Disorders (HIBR-ACHD)
Olivia Croweak - 0livia.croweak@cchmc.org
ALL
16 years and over
NCT07477197
Inclusion Criteria:
• Any person ≥ 16 years-old suspected of having or diagnosed with congenital heart disease (CHD), other cardiovascular disease (CVD), pulmonary hypertension, connective tissue disease, or genetic syndrome/diagnosis.
• Additionally, a cohort (Control group A) of control subjects will be enrolled, again ≥16 years-old, self-reported non-smokers without a known history of diabetes mellitus, myocardial infarction, stroke, heart failure, or chronic kidney disease. These controls will be either:
• A family member or other person accompanying a patient to a clinical encounter; or,
• A volunteer recruited via an advertisement; or,
• Another person who volunteers to enroll in HIBR-ACHD.
• A cohort (Control group B) of comparison subjects who do not have CHD, but have a diagnosis of heart failure or pulmonary hypertension.
Exclusion Criteria:
* Unable to provide informed consent/assent personally or via a legal guardian.
* Considered unsafe to collect the biospecimen determined by either a clinical provider or an HIBR-ACHD investigator.
* Overnight hospitalization for non-obstetric reason with discharge in the prior 30 days. Adult Congenital Heart Disease, Pulmonary Hypertension, Connective Tissue Disease, Other Cardiovascular Conditions
ACHD, Adult Congenital Heart Disease